COVID-19: Screening Antiviral Drugs Using SARS-CoV-2 Infection Models
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Researchers from Queen’s University Belfast will screen approximately 1,000 drugs, which have already received regulatory approval for other indications, to ascertain if they can reduce virus infection or replication and virus-induced inflammatory responses in airway epithelial cell models and to determine if they can therefore be repurposed to treat COVID-19 patients.
We recently spoke to Ultan F. Power, Ph.D., and Ken Mills, Ph.D., of Queen’s University Belfast to learn more about the library of drugs they are testing and the cell models they are using. We also discuss how long testing will take and what the next steps will be if they do identify promising drugs from those they have screened.
Q: Could you tell us more about some of the drugs that are to be tested?
A: The drugs that are to be tested represent a mixture of antiviral agents already in use and a library of agents that have been approved for clinical use by the US Food and Drug Administration (FDA). These drugs include agents used the for the treatment of, amongst other diseases, cancer, dementia, cardiovascular disorders, skin infections. The premise is that as these drugs are already used within the population for other indications, they have been deemed to be safe and the identification of these agents for COVID-19 means that they would not require rigorous early phase testing for toxicity and safety.
Q: How was the library of 1,000 compounds generated?
A: As indicated above, the 1,000 agents represent the approved FDA agents and some other selected agents that current research has indicated might have some impact. We hope to identify which combinations might be relevant though our screening methodology that accelerates the process by decreasing the number of comparisons from over 500,000 to around 5,000. Thus, reducing cost and time.
Q: Could you elaborate on the airway epithelial cell models you will be using?
A: We will undertake initial screening on appropriate monolayer cell lines. When promising drugs are identified we will validate their activities using 3D air liquid interface (ALI) cultures of well-differentiated primary airway epithelial cells.
Q: How long will it take to test the drug compounds in the epithelial cell models?
A: This is a 12-month project and will include set up of the SARS-CoV-2 infection models (monolayer and 3D cultures), high-throughput drug screening, and validation on the 3D ALI cultures.
Q: If promising compounds are identified what are the next steps? What “further testing” will need to be conducted?
A: Because the drugs we are testing are already FDA-approved, our goal is the proceed as quickly as possible into clinical trials. We are already in communication with a new UK-wide COVID-19 consortium of academic institutions, clinical research organizations (CROs) and pharmaceutical companies, whose overarching aim is to accelerate clinical development and approval of promising drug candidates to treat COVID-19.
Q: It must be challenging continuing lab work amidst the pandemic, what approaches have you and your team taken to adopt the “new normal”?
A: We are the only laboratory in operation in the university at the moment. Therefore, the number of individuals working together within the research team is quite small. Therefore, social distancing is very easy to implement. However, when we work in Biosafety Level (BSL) 3 conditions, the risk of infection is virtually zero, as all staff are required to use appropriate personal protective equipment and adhere to strict and rigorous practices while in the BSL 3 laboratory. Furthermore, team members are also working from home when not needed in the laboratory.
Ultan F. Power and Ken Mills were speaking to Laura Elizabeth Lansdowne, Senior Science Writer for Technology Networks.
